Effects of the Ethanol and Ethyl Acetate Extracts of Terminalia chebula Retz. on Proliferation, Migration, and HIF-1α and CXCR-4 Expression in MCF-7 Cells: an In Vitro Study.

Over recent years, much attention has been devoted to the field of screening natural products and/or their novel structures because of reversing cancer progression. The current research work was intended to explore the cytotoxic activity of ethanol and ethyl acetate extracts of dried fruit of Terminalia chebula Retz. (T. chebula) in MCF-7 cell line. High-performance thin-layer chromatographic (HPTLC) method and Folin-Ciocalteu colorimetric techniques were performed. Anti-proliferative activities of T. chebula fruit extracts on the MCF-7 cell line were evaluated using MTT assay. Effects of both extracts on the migration of MCF-7 cells and the size of MCF-7-derived spheroids were also evaluated. Moreover, antioxidant properties were measured by DPPH and FRAP methods. Western blotting was used to measure the HIF-1α and CXCR-4 protein levels. Chebulagic acid, gallic acid, chebulinic acid, and ellagic acid were found as major compounds in both extracts. The total phenolic contents based on gallic acid equivalent (GAE) in the ethanol and ethyl acetate extracts of T. chebula were found to be 453.68 ± 0.31 and 495.12 ± 0.43 mg GAE/g dry weight of the extract, respectively. Both extracts exerted a significant dose- and time-dependent cytotoxicity effect on MCF-7 cells. They also had a marked negative effect on the average size of MCF-7-derived spheroids and their migration rate. None of the extracts exhibited stronger antioxidant activities than vitamin C. Furthermore, both extracts at a concentration of 125 µg/ml could meaningfully decrease the expression levels of HIF-1α and CXCR-4 in MCF-7 cells. These data represent that T. chebula may be a valuable medicinal resource in the regulation of breast cancer proliferation, growth, and metastasis.

Naringenin attenuates cell viability and migration of C6 glioblastoma cell line: a possible role of hedgehog signaling pathway.

OBJECTIVE: Gliomas are the most prevalent type of malignant primary brain tumors. Despite the availability of several treatment modalities, these tumors have poor prognostic features. Aberrant Hedgehog (Hh) signaling has been found to be implicated in the development of numerous malignancies including gliomas. Naringenin appears to have anti-proliferative and anti-cancer properties. However, there is no report describing its effects via the Hh signaling pathway on the C6 glioblastoma cell line. The current study was set to examine the anti-cancer effects of naringenin on C6 cells in order to determine the effect of this compound on the Hh signaling pathway. METHODS: The anti-proliferative and apoptotic effects of naringenin against C6 and 3T3 fibroblast cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin-V/PI dual staining assay, respectively. The effect of naringenin on the migration of C6 cells was evaluated by the migration scratch assay. To assess the anti-cancer effect of naringenin on the Hh signaling pathway, the expression of Gli-1, Smo, and Sufu at protein levels in C6 cells was analyzed using western blotting. RESULTS: The obtained data indicated that naringenin exerted higher cytotoxicity against C6 cells (IC50 value of 114 ± 3.4 µg/mL) than normal 3T3 fibroblasts (IC50 value of 290 ± 7 µg/mL). Naringenin (114 µg/mL) also induced stronger apoptotic effects on C6 cells than 3T3 cells after 24 h of incubation. Furthermore, naringenin at a concentration of 114 µg/mL and a lower concentration of 60 µg/mL inhibited the migration of the C6 cell line. In addition, naringenin at a concentration of 114 µg/mL significantly decreased the expression of Gli-1 and Smo and elevated the expression of Sufu at the protein level in the C6 cell line. CONCLUSION: These data represent that naringenin may have a potential effect on the management of the proliferation and metastasis of malignant gliomas by inhibiting the Hh signaling pathway.

Synthesis, characterization and biocompatibility of polypyrrole/Cu(II) metal-organic framework nanocomposites.

The main objective of composite science is to fabricate new materials with desired properties such as high chemical, mechanical, and/or biological performances. In this research, new conductive nanocomposites of copper metal-organic frameworks (Cu-MOF) and polypyrrole (PPy) were fabricated with the aim of exploiting the electrical conductivity of polypyrrole and the porosity of MOFs in the final products. The prepared compounds (PPy/x%Cu-MOF, x = 20, 50, and 80) were investigated by FTIR, PXRD, SEM, TEM, DLS, BET, EDS mapping, cyclic voltammetry (CV), and zeta potential (ξ) measurements. Spherical morphology was confirmed by SEM and TEM analysis. The PPy/80%Cu-MOF nanocomposite showed the highest ξ potential (-40 mV), demonstrating the stability of dispersed particles. The CV results revealed that the nanocomposites have higher capacitance in comparison to the pure materials. In vitro degradation of the as-prepared compounds in simulated body fluid (SBF) was studied by EIS (electrochemical impedance spectroscopy) and Tafel polarization tests. Furthermore, in vitro biocompatibility of the PPy/x%Cu-MOF composite was evaluated on a group of cells including 3T3 fibroblasts, MCF-7 breast cancer cells, J774.A1 macrophages and red blood cells (RBCs). Viability of 3T3 fibroblasts, MCF-7, and J774.A1 cells, by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, was dependent on Cu-MOF percent and amount of composites. Hemolytic assay for RBCs exposed to different amounts of the PPy/x%Cu-MOF composites showed hematological toxicity less than 5% in most concentrations. In addition, to investigate pro-inflammatory activity, J774.A1 macrophages were exposed to non-toxic concentrations of the PPy/x%Cu-MOF and no significant change in the expression of two inflammatory genes COX-2 and iNOS was observed. Injection of the PPy/x%Cu-MOF (5 mg kg-1) into bloodstream of mice did not increase liver damage marker enzymes alanine transaminase (ALT) and aspartate transaminase (AST) level in serum 1 week post injection. Moreover, we observed slight but not significant increase in serum copper level in mice 1 week after injection. According to the results, the PPy/x%Cu-MOF nanocomposites exhibited a good in vitro and in vivo biocompatibility without inducing pro-inflammatory responses in macrophages and show promising potential for different biomedical applications such as biosensors and drug delivery. The release of curcumin from curcumin-loaded PPy/x%Cu-MOF nanocomposites was detectable in plasma of mice 4 days after administration.